The world of physics covers a wide range of length scale: from nanometer scale atoms all the way up to stars and galaxies. When speaking of physics, people tend to think of things that are not “alive”, such as material physics, particle physics, astronomy, etc.

In the last decade, a new area of physics called active matter physics has arisen. To better understand active matter physics, it is helpful to introduce a similar field, soft matter physics. Soft matter physics mainly studies the group behavior of particles with the size of several micrometers. Behavior of a system at such a small size is largely determined by thermal dynamics. Glass, soft gels, granular material are all studied by soft matter physics.

Active matter physics, on the other hand, is very similar to soft matter physics, since it also mainly focuses on studying the group behavior of a system that arises from the interactions of “particles”. However, one of the crucial differences between active matter physics and soft matter physics is that active matter physics studies particles that are “active”, which means that by consuming energies from the environment, they can produce self-motility. Systems studied by active matter physics can range from bird flocks (Fig.1) to cytoskeleton structures inside cells (Fig.2).

Studying active matter physics provides another perspective for understanding the emerging behavior in a biological system. For instance, there has been work done on simulating cell motion in densely packed tissues. Physicists using tools from statistical mechanics have successfully simulated how cells move around inside tissues and have found that there is a transition where cell motility changes from liquid-like flowing into solid-like jiggling around its initial position. They are able to plot out the phase diagram of such transitions in a space determined by three parameters: cell moving speed, persistence time along a single cell track, and a shape index that characterizes the competition between cell-cell adhesion and cortical tension. Such results provide an insight into the understanding of similar solid-to-liquid transition observed in cancer progressions.

About the author: Yu Shi is a 4th year PhD student in the Department of Physics & Astronomy at Johns Hopkins University. He is in Prof. Daniel Reich’s lab, and his current works focus on studying dynamic properties of actin-myosin system inside cells using micro-patterned substrate.

Professor Chia-Ling Chien, a condensed matter physicist at Johns Hopkins University and long-time affiliated faculty member of INBT, will receive the prestigious 2015 IUPAP Magnetism Award and Néel Medal from the Commission on Magnetism within the International Union of Pure and Applied Physics. Chien directs the Nanostructured Materials Lab in the Department of Physics and Astronomy at the Krieger School of Arts and Sciences.

The award, which will be presented this summer, recognizes Chien’s pioneering discoveries in magnetic materials and nanostructures. The IUPAP Magnetism Award and Néel Medal are awarded every three years to a scientist who has made extraordinary contributions to the field of magnetism. The award is the highest honor bestowed by the IUPAP Commission on Magnetism.

Congratulations to Dr. Chien.

Read more about Dr. Chien’s award and research in this story on the JHU Hub.

Imagine being able to drop a toothpick on the head of one particular person standing among 100,000 people in a sports stadium. It sounds impossible, yet this degree of precision at the cellular level has been demonstrated by researchers affiliated with The Johns Hopkins University Institute for NanoBioTechnology. Their study was published online in June in Nature Nanotechnology.

The team used precise electrical fields as “tweezers” to guide and place gold nanowires, each about one-two hundredth the size of a cell, on predetermined spots, each on a single cell. Molecules coating the surfaces of the nanowires then triggered a biochemical cascade of actions only in the cell where the wire touched, without affecting other cells nearby. The researchers say this technique could lead to better ways of studying individual cells or even cell parts, and eventually could produce novel methods of delivering medication.

Indeed, the techniques not relying on this new nanowire-based technology either are not very precise, leading to stimulation of multiple cells, or require complex biochemical alterations of the cells. With the new technique the researchers can, for instance, target cells that have cancer properties (higher cell division rate or abnormal morphology), while sparing their healthy neighbors.

“One of the biggest challenges in cell biology is the ability to manipulate the cell environment in as precise a way as possible,” said principal investigator Andre Levchenko, an associate professor of biomedical engineering in Johns Hopkins’ Whiting School of Engineering. In previous studies, Levchenko has used lab-on-a-chip or microfluidic devices to manipulate cell behavior. But, he said, lab-on-a-chip methods are not as precise as researchers would like them to be. “In microfluidic chips, if you alter the cell environment, it affects all the cells at the same time,” he said.

Such is not the case with the gold nanowires, which are metallic cylinders a few hundred nanometers or smaller in diameter. Just as the unsuspecting sports spectator would feel only a light touch from a toothpick being dropped on the head, the cell reacts only to the molecules released from the nanowire in one very precise place where the wire touches the cell’s surface.

With contributions from Chia-Ling Chien, a professor of physics and astronomy in the Krieger School of Arts and Sciences, and Robert Cammarata, a professor of materials science and engineering in the Whiting School, the team developed nanowires coated with a molecule called tumor necrosis factor-alpha (TNF?), a substance released by pathogen-gobbling macrophages, commonly called white blood cells. Under certain cellular conditions, the presence of TNF? triggers cells to switch on genes that help fight infection, but TNF? also is capable of blocking tumor growth and halting viral replication.

Exposure to too much TNF?, however, causes an organism to go into a potentially lethal state called septic shock, Levchenko said. Fortunately, TNF? stays put once it is released from the wire to the cell surface, and because the effect of TNF? is localized, the tiny bit delivered by the wire is enough to trigger the desired cellular response. Much the same thing happens when TNF? is excreted by a white blood cell.

Additionally, the coating of TNF? gives the nanowire a negative charge, making the wire easier to maneuver via the two perpendicular electrical fields of the “tweezer” device, a technique developed by Donglei Fan as part of her Johns Hopkins doctoral research in materials science and engineering. “The electric tweezers were initially developed to assemble, transport and rotate nanowires in solution,” Cammarata said. “Donglei then showed how to use the tweezers to produce patterned nanowire arrays as well as construct nanomotors and nano-oscillators. This new work with Dr. Levchenko’s group demonstrates just how extremely versatile a technique it is.”

To test the system, the team cultured cervical cancer cells in a dish. Then, using electrical fields perpendicular to one another, they were able to zap the nanowires into a pre-set spot and plop them down in a precise location. “In this way, we can predetermine the path that the wires will travel and deliver a molecular payload to a single cell among many, and even to a specific part of the cell,” Levchenko said.

During the course of this study, the team also established that the desired effect generated by the nanowire-delivered TNF? was similar to that experienced by a cell in a living organism.

The team members envision many possibilities for this method of subcellular molecule delivery. “For example, there are many other ways to trigger the release of the molecule from the wires: photo release, chemical release, temperature release. Furthermore, one could attach many molecules to the nanowires at the same time,” Levchenko said. He added that the nanowires can be made much smaller, but said that for this study the wires were made large enough to see with optical microscopy.

Ultimately, Levchenko sees the nanowires becoming a useful tool for basic research. “With these wires, we are trying to mimic the way that cells talk to each other,” he said. “They could be a wonderful tool that could be used in fundamental or applied research.” Drug delivery applications could be much further off. However, Levchenko said, “If the wires retain their negative charge, electrical fields could be used to manipulate and maneuver their position in the living tissue.”

The lead authors for this Nature Nanotechnology article were Fan, a former postdoctoral fellow in the departments of materials science and engineering and in physics and astronomy; and Zhizhong Yin, a former postdoctoral fellow in the Department of Biomedical Engineering. The co-authors included Raymond Cheong, a doctoral student in the Department of Biomedical Engineering; and Frank Q. Zhu, a former doctoral student in the Department of Physics and Astronomy.

Regarding the faculty members’ participation, Chien led the group that developed the electric tweezers technique and collaborated with Levchenko on its biological applications.

The research was funded by the National Science Foundation and the National Institutes of Health.

The fact that cancer cells frequently re-emerge after initial therapeutic attempts has dogged the efforts of oncologists to save patients’ lives for decades. According to Princeton physicist, Robert H. Austin, cancer cell resistance is primarily a biological reaction to stress and “one of the great unsolved, and deadly, problems in oncology.”

On Thursday, February 4, Austin will discuss, “The Physics of Cancer,” during a 3 p.m. joint colloquium hosted by Johns Hopkins University departments of Physics and Astronomy and Biophysics in the Schafler auditorium of the Bloomberg Center on the Homewood campus. The talk is free and open to the public.

Austin is principal investigator for Princeton’s Physical Science-Oncology Center and a trans-network partner with Johns Hopkins Engineering in Oncology Center, both of which are National Cancer Institute funded organizations.

Austin will address the general principles of physics, ecology, and biology and why recurrence of resistant cancer cells seems to be a universal phenomenon in cancer. He says that “evolution in small, stressed habitats is key to the rapid and inevitable re-emergence of resistance of cancer cells” (and) “that modern techniques of physical probes, genomics, proteomics and nanotechnology will allow us to analyze the evolutionary path of these emergent resistant cells.”

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